苏郁胶囊对慢性应激抑郁模型大鼠海马神经细胞凋亡的影响

The effect of Suyu capsule on nerve cell apoptosis in hippocampus of the depression model rats

目的探究苏郁胶囊抗抑郁的作用机制。方法将96只Open-F ield评分相近的成年SD雄性大鼠随机分为正常组、模型组、苏郁胶囊高、中、低剂量组(22.8g/kg、11.4g/kg、5.7g/kg)及氯米帕明组(0.02g/kg)。采用长期不可预见中等强度应激结合孤养造成大鼠抑郁模型。Open-F ield法和糖水消耗实验测定各组大鼠的行为变化;用TUNEL试剂盒检测海马CA3区神经细胞凋亡情况,免疫组化法检测Bc l-xl蛋白的表达;应用钙离子荧光指示剂Fura-2/AM测定海马突触体内游离Ca2+浓度。结果与正常组比较,模型组大鼠出现明显的行为异常,糖水消耗明显减少;海马CA3区TUNEL阳性细胞数增加明显,Bc l-xl蛋白表达减少明显;海马突触体内游离Ca2+浓度明显升高。苏郁胶囊高中治疗组能明显增加抑郁大鼠的糖水消耗量,改善其行为异常;苏郁胶囊高中低治疗组能明显减少海马CA3区TUNEL阳性细胞数,上调海马CA3区Bc l-xl蛋白表达,减少海马突触体内游离Ca2+浓度,并具有一定的量效关系。结论苏郁胶囊能改善大鼠的抑郁样行为;抑制抑郁大鼠海马神经细胞凋亡。其可能与苏郁胶囊抑制海马神经细胞外Ca2+大量内流,阻止Ca2+超载,上调海马Bc l-xl蛋白表达相关。

OBJECTIVE This study examine the possible mechanism of Suyu capsule for antidepressive action.METHODS 96 male SD rats were separated randomly into 6 groups including the control group,the model group,Anafranil group and three other groups under the treatment of suyu capsule with the doses of 22.8g/kg,11.4g/kg,5.7g/kg respectively.The model was established by separation and chronic unpredictable mild stimulation.The behavioral outcome of the rats were measured by crossing score,rearing score of the open-field method in addition to the records of sweet water consumption of rats.On the other hand,cell apoptosis of rats in CA3 region of hippocampus neurons were examined by TUNEL while the expression of Bcl-xl protein were detected by an immunohistochemistry method.The concentration of Ca^(2+) ion in the hippocampal synaptic was determined by fluorimetry. RESULTS Comparing to those in the control group,rats in the model group showed obvious dystrophy with much lower sweet water consumption.Further,the numbers of the positive cells in the sub-region of CA3 region of hippocampus by TUNEL were obviously increased in contrast to an apparent decrease in the expression of Bcl-xl protein in the same region.In addition,Ca^(2+) ion in hippocampal synaptic was found to be increased.On the other hand,Suyu capsule(22.8g/kg,11.4g/kg)when used to improve the behavioral outcome of rats with an increase in sweet water consumption and improvements in the crossing scores and rearing scores of the depression model rats.Suyu capsule(22.8g/kg,11.4g/kg,5.7g/kg) was found to decrease the numbers of TUNEL positive cells but at the same time increase the expression of Bcl-xl protein in the CA3 region of hippocampus.Further,the same treatments were also found to decrease Ca^(2+) ion in hippocampal synaptic with dose-effect relationship.CONCLUSION Suyu capsule can reverse all the symptoms of the depression and reduce nerve cell apoptosis in hippocampus of in the rats of the mode depression group.The effects appear to be brought about by reducing the secretion of Ca^(2+) ion and increasing expression of Bcl-xl protein in the subregion of hippocampus.